The studies in progress constitute an extension of our investigation of the pathogenesis and pathophysiology of clinical disorders of renal acidification. In patients with Type 1 (distal) renal tubular acidosis (RTA), studies have been designed to determine: (a) whether the impairment of H plus -secretory process or a limitation on its ability to generate transepithelial H plus concentration gradients; (b) whether primary disturbances occur in renal tubular transport of potassium and/or chloride. In patients with type 2 (proximal) RTA, studies have been designed to investigate the mechanism of the reported ameliorative effect of hydrochlorothiazide. In infants and children presenting with renal hyperchloremic acidosis associated with persistent hyperkalemia (so-called type 4 RTA), studies have been designed to investigate the physiological character and natural history of the renal acidification dysfunction. In these studies, and in the studies described in patients with types 1 and 2 RTA, the functional activity and pathogenetic role of the renin-angiotensin-aldosterone system will be defined, and in the patients with type 2 RTA the role of renal prostaglandins. Additional studies have been designed to investigate the pathogenesis of renal hyperchloremic metabolic acidosis and hyperkalemia associated with chronic renal insufficiency. The role of aldosterone deficiency in renal acid-base homeostasis in patients without renal diseases, and the effects of dietary potassium depletion on renal acid-base homeostasis.